Box-Behnken study design for optimization of bicalutamide-loaded nanostructured lipid carrier: stability assessment.

Bicalutamide (BCM) is an anti-androgen drug used to treat prostate cancer. In this study, nanostructured lipid carriers (NLCs) were chosen as a carrier for delivery of BCM using Box-Behnken (BB) design for optimizing various quality attributes such as particle size and entrapment efficiency which is very critical for efficient drug delivery and high therapeutic efficacy. Stability of formulated NLCs was assessed with respect to storage stability, pH stability, hemolysis, protein stability, serum protein stability and accelerated stability. Hot high-pressure homogenizer was utilized for formulation of BCM-loaded NLCs. In BB response surface methodology, total lipid, % liquid lipid and % soya lecithin was selected as independent variable and particle size and %EE as dependent variables. Scanning electron microscopy (SEM) was done for morphological study of NLCs. Differential scanning calorimeter and X-ray diffraction study were used to study crystalline and amorphous behavior. Analysis of design space showed that process was robust with the particle size less than 200 nm and EE up to 78%. Results of stability studies showed stability of carrier in various storage conditions and in different pH condition. From all the above study, it can be concluded that NLCs may be suitable carrier for the delivery of BCM with respect to stability and quality attributes.

Design of surface tailored carboxymethyl dextran-protein based nanoconjugates for paclitaxel: Spectroscopical characterizations and cytotoxicity assay.

Paclitaxel (PTX) is an essential anticancer drug from the biopharmaceutical classification system (BCS) class IV. Unfortunately, PTX has some drawbacks including low solubility, cell toxicity, adverse cell reaction, etc. Therefore, folic acid (FA) tailored carboxymethyl-dextran (CMD), and bovine serum albumin (BSA) mediated nanoconjugates of paclitaxel (PTX) (FA-CMD-BSA-PTX) were designed. At first, esterification reaction between FA and CMD resulted in FA-CMD conjugate whereas FA-CMD-BSA conjugate was synthesized via the Maillard reaction. Finally, FA-CMD-BSA conjugates of PTX were achieved via hydrophobic interaction and gelation of BSA. Herein, heating offers the gelation of BSA that furnishes the cross-linking wherein PTX gets fixed inside BSA. Thermogram of FA-CMD-BSA-PTX showed the absence of PTX peak that concluding PTX has been molecularly dispersed in polymer matrix and entrapment inside polymeric conjugate. As an effect, surface decorated FA-CMD-BSA-PTX showed low hemolytic toxicity over free PTX. Cytotoxicity assay on A549 human lung cancer cells shows cell viability decreased from 60 % to 10 % with increasing concentration from 1 to 5 µg/mL. In conclusion, CMD facilitates the circulation time of PTX and BSA acts as a carrier to target tumor locations effectively. The nano-conjugate formulation significantly reduces toxicity and can be used for the treatment of lung cancer.

Development of pH-Dependent Nanospheres for Nebulisation- In vitro Diffusion, Aerodynamic and Cytotoxicity Studies.

The aim of this work was to evaluate the in vitro performance of nebulized nanosuspension formulation when nebulized using ultrasonic nebulizer. The present investigation deals with successful formulation of Beclomethasone dipropionate loaded HPMCP nanospheres prepared by solvent evaporation technique using PEG 400 as a stabilizer. Beclomethasone dipropionate is a water insoluble drug molecule was encapsulated in HPMCP nanospheres to have pH dependent solubility at basic pH for targeted drug delivery in lung and studied for in vitro cytotoxicity and immediate release capability. The synthesized nanospheres were characterized through drug excipient compatibility, surface topography; mean particle size , zeta potential, PDI, entrapment efficiency and drug loading, in vitro diffusion, aerodynamic, in vitro cytotoxicity and stability studies. The mean particle size and PDI of the optimized batch (F1) had 197.6±0.40 nm and 0.324 ±0.35, respectively. The % entrapment efficiency and % drug loading was found to be 86.56±1.32 and 8.30±0.27, respectively. The optimized batch F1 showed % cumulative drug release 94.77±0.24 at 1 h. The formulation showed cell viability up to 91.28%. It can be concluded that, Beclomethasone dipropionate loaded HPMCP nanospheres was found to be safe, stable with significant increase in solubility and bypass the liver.